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Mitochondrial Oxidative Phosphorylation (OXPHOS) Dysfunction:
A newly emerging category of Autistic Spectrum Disorder
Information for Primary Care Physicians
Compiled By: Dr. Susan Leib, M.D. and Alyssa Davi (parent/child advocate)
Presented at pediatric conference on December 2009, updated May 2010
Mitochondrial Awareness Week took place on September 20-26. Mitochondrial disease is
currently greatly under-recognized. Disorders of energy metabolism are thought to affect roughly
1:4000 people and recent statistics suggest it might be as high as 1:1000 people.
Mitochondrial Oxidative Phosphorylation (known as OXPHOS) is emerging as a new category of
autistic spectrum disorder (ASD) per Dr. Natowicz, a geneticist, at the Cleveland Clinic. Dr.
John Shoffner, one of the leading diagnosticians in the field of mitochondrial medicine has said,
“When you consider the frequency of autism in the general population, and you take 20% of that
as a rough estimate of the proportion of children that may have these biochemical markers (of
mitochondrial dysfunction), it begins to raise some interesting questions about how to approach
diagnosis, mechanism of disease, and patient management in what could turn out to be significant
numbers of individuals.” (from “Mitochondrial Dysfunction May Play a Role in Autism
Spectrum Disorders Etiology”)
“Recently, Oliveira and colleagues published a population-based survey of school age children
with ASD. They found that 7% of those who were fully tested met criteria for definite
mitochondrial respiratory chain disorders and were also clinically indistinguishable from other
children with ASD.” (from “Mitochondrial Disease in Autism Spectrum Disorder Patients: A
Cohort Analysis”)
For thousands of children that have been diagnosed ASD, this could mean new treatment options.
Although OXPHOS is not thought to be curable at this time, children that have OXPHOS
symptoms can be helped and/or managed by taking a “mito. cocktail”. If OXPHOS children can
be identified sooner, medications and supplements would then be made available to a whole
group of children (ASD and non-ASD children with atypical or unusual clinical presentations)
that may currently be getting no biochemical treatment or metabolic support.
There is currently very little knowledge of these disorders in the general medical community as
they were once thought to be rare. Knowing that this is no longer true, the top pediatric
specialists in the field of mitochondrial medicine are now asking for early screening to occur by
primary care physicians. The road to a diagnosis is often a long and difficult one for many
families as the presentation of these disorders is often varied and complex. “It is hoped that
greater familiarity among primary care physicians with the manifestations of mitochondrial
disease will facilitate proper diagnosis and management of this growing cohort of pediatric
patients across all specialties” (from Mitochondrial Disease: A Practical Approach for Primary
Care Physicians, www.mitosoc.org)
Mitochondrial disease should be considered in any patient with unexplained multi-system
involvement and an unusual clinical presentation or regressive autism. Fatigue is a hallmark
symptom.
Mitochondria are the “power plants” of the body. The organs in the body that require the most
energy are the brain, muscle, “The parts of the body that need the most energy, such as the heart,
brain, muscles and lungs are the most affected by mitochondrial disease. The affected individual
may have strokes, seizures, gastro-intestinal problems (reflux, severe vomiting, constipation,
diarrhea), swallowing difficulties, failure to thrive, blindness, deafness, heart and kidney
problems, muscle failure, heat/cold intolerance, diabetes, lactic acidosis, immune system
problems and liver disease. An undiagnosed child may exhibit feeding problems, be unable to
fight typical childhood infections or have repeated infections and fevers without a known origin.
A “red flag” for mitochondrial disease is when a child has more than 3 organ systems with
problems or when a “typical” disease exhibits atypical qualities. (from www.UMDF.org)
The Mitochondrial Medicine Society lists the following as red flag symptoms (from
www.mitosoc.org):
Additional possible symptoms can be found at:
http://www.umdf.org/site/c.otJVJ7MMIqE/b.5692883/k.C0C7/Possible_Symptoms.htm
http://www.umdf.org/site/c.dnJEKLNqFoG/b.3042207/k.C54C/Symptoms_of_Mitochondrial_Cy
topathies.htm
The Mitochondrial Medicine Society lists the following as initial tests (from
www.mitosoc.org)
:
Laboratory evaluation of patients with possible mitochondrial disease from the United
Mitochondrial Disease Foundation
http://www.umdf.org/site/c.otJVJ7MMIqE/b.5703929/k.90BE/Lab_Evaluation.htm
The Mitochondrial Medicine Society lists the following as Findings Suggestive of Mitochondrial
Dysfunction (from www.mitosoc.org):
The following links are for Primary Care Physicians to help with initial testing, referrals,
diagnosis and management of a patient with suspected Mitochondrial Disease.
A Modern Approach to the Treatment of Mitochondrial Disease
http://www.springerlink.com/content/d872354q672090mq/?p=fd9ba0ec0d2a4789b9d74c7daf763
fa0&pi=2
Mitochondrial Disease: A Practical Approach for Primary Care Physicians
http://pediatrics.aappublications.org/cgi/content/full/120/6/1326
Clinicians Guide to the management of Mitochondrial Disease: A Manual for Primary Care
Providers
http://www.mitoaction.org/guide/table-contents
Mitochondrial and Metabolic Disorders- A Primary Care Physician’s Guide
http://biochemgen.ucsd.edu/mmdc/ep-toc.htm
Dr. Mark Korson, Chief of the Metabolic Program at Tufts New England Medical Center, speaks
about Mitochondrial Disease and Patient Challenges (5 minute video)
http://www.youtube.com/mitoaction#play/all/F38FD8F6D9124E1B-all/1/-zf3eYRGpko
Related OXPHOS research articles:
Mitochondrial Dysfunction May Play a Role in Autistic Spectrum Disorders Etiology
http://www.medscape.com/viewarticle/573004
Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2584230
Oxidative Phosphorylation (OXPHOS) Defects in Children with Autistic Spectrum Disorders
http://www.abstracts2view.com/aan2008chicago/view.php?nu=AAN08L_IN1-1.004
Fever Plus Mitochondrial Disease Could Be Risk Factors for Autistic Regression
http://www.ncbi.nlm.nih.gov/pubmed/19773461
Mitochondrial Dysfunction in Autism Spectrum Disorders: A Population Based Study
http://www.ncbi.nlm.nih.gov/pubmed/15739723?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pu
bmed.Pubmed_ResultsPanel.Pubmed_RVBrief
Relative Carnitine Deficiency in Autism
http://www.ncbi.nlm.nih.gov/pubmed/15679182
Websites for further information:
www.mitosoc.org
www.mitoaction.org
www.umdf.org
List of Mitochondrial Disease Doctors/Specialists (with hospital affiliation) can be found at:
http://www.mitosoc.org/blogs/diagnosis/providers